The Present Indication and Future of Deep Brain Stimulation

The use of electrical stimulation to treat pain in human disease dates back to ancient Rome or Greece. Modern deep brain stimulation (DBS) was initially applied for pain treatment in the 1960s, and was later used to treat movement disorders in the 1990s. After recognition of DBS as a therapy for central nervous system (CNS) circuit disorders, DBS use showed drastic increase in terms of adaptability to disease and the patient’s population. More than 100,000 patients have received DBS therapy worldwide. The established indications for DBS are Parkinson’s disease, tremor, and dystonia, whereas global indications of DBS expanded to other neuronal diseases or disorders such as neuropathic pain, epilepsy, and tinnitus. DBS is also experimentally used to manage cognitive disorders and psychiatric diseases such as major depression, obsessive-compulsive disorder (OCD), Tourette’s syndrome, and eating disorders. The importance of ethics and conflicts surrounding the regulation and freedom of choice associated with the application of DBS therapy for new diseases or disorders is increasing. These debates are centered on the use of DBS to treat new diseases and disorders as well as its potential to enhance ability in normal healthy individuals. Here we present three issues that need to be addressed in the future: (1) elucidation of the mechanisms of DBS, (2) development of new DBS methods, and (3) miniaturization of the DBS system. With the use of DBS, functional neurosurgery entered into the new era that man can manage and control the brain circuit to treat intractable neuronal diseases and disorders.     

Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: the search for a valid target

Obsessive-compulsive disorder (OCD) is a common psychiatric disease that is marked by recurring, anxiety-provoking thoughts (obsessions) accompanied by repetitive and time-consuming behaviors (compulsions). Among the controversies in the OCD literature is the issue of the origin of the disease and whether brain changes observed with modern imaging techniques are the causes or results of OCD behaviors and thoughts. These issues remain unresolved; however, significant strides have been made in understanding the illness from both phenomenological and pathophysiological perspectives. The current staple of OCD management remains pharmacological in nature and often occurs in conjunction with cognitive behavioral therapy. Refractory cases, however, are occasionally referred for neurosurgical consultation, and several procedures have been examined. Success in the treatment of Parkinson's disease, the reversibility of the therapy, and a relatively safe side-effect profile have allowed deep brain stimulation (DBS) to be examined as an alternative treatment for some psychiatric conditions. Here we assess the possibility of applying DBS to the treatment of OCD. Morphological, functional metabolic, and volumetric data point to several brain regions that are important to the etiology and maintenance of OCD. Converging evidence from the genetics and neurocircuitry literature suggests that several subcortical structures play prominent roles in the disease. The functional modification of these structures could potentially provide symptom relief. Here, we review the ablative and DBS procedures for refractory OCD, and provide a research-driven hypothesis that highlights the ventromedial head of the caudate nucleus, and structures up- and downstream from it, as potential DBS targets for treatment-resistant disease. We hope that a research-driven approach, premised on converging evidence and previous experience, will lead to a safe and effective DBS procedure that will benefit patients who remain disabled despite presently available therapies.     

Preparing the ethical future of deep brain stimulation

Background

Deep brain stimulation is an approved and effective neurosurgical intervention for motor disorders such as PD and ET. Deep brain stimulation may also be effective in treating a number of psychiatric disorders, including treatment refractory depression and OCD. Although DBS is a widely accepted therapy in motor disorders, it remains an invasive and expensive procedure. The ethical and social challenges of DBS need further examination, and discussion and emerging applications of DBS in psychiatry may also complicate the ethical landscape of DBS.

Methods

To identify and characterize current and emerging issues in the use of DBS, we reviewed the neurosurgical literature on DBS as well as the interdisciplinary medical ethics and relevant psychological and sociological literatures. We also consulted the USPTO database, FDA regulations and report decisions, and the business reports of key DBS manufacturers.

Results

Important ethical and social challenges exist in the current and extending practice of DBS, notably in patient selection, informed consent, resource allocation, and in public understanding. These challenges are likely to be amplified if emerging uses of DBS in psychiatry are approved.

Conclusions

Our review of ethical and social issues related to DBS highlights that several significant challenges, although not insurmountable, need much closer attention. A combination of approaches previously used in neuroethics, such as expert consensus workshops to establish ethical guidelines and public engagement to improve public understanding, may be fruitful to explore.     

Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report

Obsessive-compulsive disorder (OCD) is an anxiety disorder associated with recurrent intrusive thoughts and repetitive behaviors. Although conventional pharmacological and/or psychological treatments are well established and effective in treating OCD, symptoms remain unchanged in up to 30% of patients. Deep brain stimulation (DBS) of the anterior limb of the internal capsule has recently been proposed as a possible therapeutic alternative in treatment-resistant OCD. In the present study, the authors tested the hypothesis that DBS of the ventral caudate nucleus might be effective in a patient with intractable severe OCD and concomitant major depression. Psychiatric assessment included the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), and the Global Assessment of Functioning (GAF) Scale for determining the symptom severity of OCD, depression, and anxiety as well as the quality of pychosocial and occupational functioning, respectively. Neuropsychological assessment consisted of a wide range of tests primarily exploring memory and executive functions. Deep brain stimulation of the ventral caudate nucleus markedly improved symptoms of depression and anxiety until their remission, which was achieved at 6 months after the start of stimulation (HDRS < or = 7 and HARS < or = 10). Remission of OCD (Y-BOCS < 16) was also delayed after 12 or 15 months of DBS. The level of functioning pursuant to the GAF scale progressively increased during the 15-month follow-up period. No neuropsychological deterioration was observed, indicating that DBS of the ventral caudate nucleus could be a promising strategy in the treatment of refractory cases of both OCD and major depression.     

Deep brain stimulation devices: a brief technical history and review

Deep brain stimulation (DBS)—a broadly accepted therapeutic modality with tens of thousands of patients currently implanted—is the application of implantable electrical stimulation devices to treat neurological disorders. Approved indications include involuntary movement disorders; investigational applications include epilepsy, selected psychiatric disorders, and other conditions. DBS differs fundamentally from functional electrical stimulation and sensory prosthetics in that DBS therapies do not substitute for or replace injured tissues, organs, or body functions. DBS—targeted to particular brain nuclei or pathways that are specific for the disorder under treatment—influences brain function and behavioral output in ways that can relieve symptoms and improve the overall functioning of the patient. We will briefly review the history and present status of DBS from a technical and device-oriented perspective, with an eye toward future advances.     

A psychiatric primer for the functional neurosurgeon

There is increasing attention in the neurosurgical literature towards surgery, specifically deep brain stimulation (DBS), for psychiatric indications. Several positive trials have spurred intense investigation and research in this area, owing to rapid advances in the neurosciences. As a result, the scope of neurosurgical practice is evolving to now include disorders that weren't traditionally in the purview of the average functional neurosurgeon. Further, functional neurosurgeons are now being charged with taking care of patients as part of a multi-disciplinary group that includes psychologists and psychiatrists. As DBS for psychiatry continues to evolve, and as further indications are explored, it is incumbent on neurosurgeons who treat these disorders to familiarize themselves with current standards of diagnosis and treatment. Just as the movement disorder surgeon should be familiar with the biology, physiology, diagnosis and treatment of Parkinson's disease, so they should become familiar with similar aspects of commonly referred psychiatric conditions. Specifically, much of the interest in the DBS literature currently surrounds major depression, obsessive-compulsive disorder and Tourette's syndrome. Here, we review the epidemiology, diagnostic criteria, hypothesized neurocircuitry and current treatments, both medical and surgical of each of these conditions to serve as a centralized, introductory primer for the practicing functional neurosurgeon.     

An approach to deep brain stimulation for severe treatment-refractory Tourette syndrome: the UK perspective

Deep brain stimulation (DBS) is an emerging therapeutic option for severe, treatment-resistant Tourette Syndrome (TS), with about 40 cases reported in the scientific literature over the last decade. Despite the production of clinical guidelines for this procedure from both European and USA centres, a number of unresolved issues still persist, mainly in relation to eligibility criteria and brain targets. The present article illustrates the UK perspective on DBS in TS and proposes consensus-based recommendations for double-blind controlled trials.     

Pediatric Factitious Disorder Perpetuated by Others: A Dermatologist’s Duty Beyond the Skin

Factitious disorders and factitious disorders imposed on another are a prevalent encounter during dermatology visits. Here, we present a case of a pediatric patient who presented with ulcer-like lesions that, based on initial biopsy, suggested an immunobullous etiology. Further exploration revealed her underlying psychiatric disorder. Dermatologists play an integral role in recognizing and initiating “nervous system” management to establish a level of trust with the patient that will ultimately allow bridging to psychiatric care. The case discussed here serves as an example of the successful diagnosis and treatment of a pediatric psychiatric patient by raising clinical suspicion, using investigative techniques, employing separate interviews and the Patient Health Questionnaire-9, and sensitively addressing the relationship between the patient, guardian, and provider within the dermatology clinic.     

A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder

OBJECT: Deep brain stimulation (DBS) of the ventral [anterior internal] capsule/ventral striatum (VC/VS) is under investigation as an alternative to anterior capsulotomy for severe obsessive-compulsive disorder (OCD). In neuroimaging studies of patients with OCD, dysfunction in the orbitofrontal and anterior cingulate cortex, striatum, and thalamus has been identified; and modulation of activity in this circuit has been observed following successful nonsurgical treatment. The purpose of the current study was to test hypotheses regarding changes in regional cerebral blood flow (rCBF) during acute DBS at the VC/VS target in patients with OCD who were participating in a clinical DBS trial. METHODS: Six patients enrolled in a DBS trial for OCD underwent positron emission tomography to measure rCBF; the rCBF measured during acute DBS at high frequency was then compared with those measured during DBS at low frequency and off (control) conditions. On the basis of neuroanatomical knowledge about the VC/VS and neuroimaging data on OCD, the authors predicted that acute DBS at this target would result in modulation of activity within the implicated frontal-basal ganglia-thalamic circuit. Data were analyzed using statistical parametric mapping. In a comparison of acute high-frequency DBS with control conditions, the authors found significant activation of the orbitofrontal cortex, anterior cingulate cortex, striatum, globus pallidus, and thalamus. CONCLUSIONS: Acute DBS at the VC/VS target is associated with activation of the circuitry implicated in OCD. Further studies will be necessary to replicate these findings and to determine the neural effects associated with chronic VC/VS DBS. Moreover, additional data are needed to investigate whether pretreatment imaging profiles can be used to predict a patient's subsequent clinical response to chronic DBS.     

Visualization of the internal globus pallidus: sequence and orientation for deep brain stimulation using a standard installation protocol at 3.0 Tesla

Background  

Deep-brain stimulation (DBS) of the internal globus pallidus (GPi) has shown remarkable therapeutic benefits for treatment-resistant neurological disorders including dystonia and Parkinson’s disease (PD). The success of the DBS is critically dependent on the reliable visualization of the GPi.     

Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: A review

Context

Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain.

Objective

To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy.

Methods

A MEDLINE search was performed using following terms: “Spinal cord injury”, “Neuropathic pain”, “Brain stimulation”, “Deep brain stimulation” (DBS), “Motor cortex stimulation” (MCS), “Transcranial magnetic stimulation” (TMS), “Transcranial direct current stimulation” (tDCS), “Cranial electrotherapy stimulation” (CES).

Results

Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation – tDCS – applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI.

Conclusion

A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.     

Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinson disease. Case report

The authors report on a patient with Parkinson disease (PD) and severe obsessive-compulsive disorder (OCD), in whom bilateral stimulation of the subthalamic nucleus (STN) was used to treat both PD and OCD symptoms. This 49-year-old man had displayed symptoms of PD for 13 years. Progressively, his motor disability became severe despite optimal medical treatment. In parallel, he suffered severe OCD for 16 years, with obsessions of accumulation and compulsions of gathering and rubbing that lasted more than 8 hours per day. Bilateral high-frequency STN stimulation was performed to treat motor disability. After surgery (at 1-year follow up), motor and OCD symptoms were dramatically improved. The pre- and postoperative Yale-Brown Obsessive-Compulsive Scale scores were 32 and 1, respectively. No additional antiparkinsonian drugs were administered. This case and other recent reports indicate that OCD symptoms can be improved by deep brain stimulation, a finding that opens new perspectives in the surgical treatment of severe and medically intractable OCD.     

Clinical problems in patient with Ehlers-Danlos syndrome and Multiple Chemical Sensitivity undergoing total thyroidectomy

Clinical practice sometimes brings to face with situations quite peculiar, potentially dangerous for the patient’s life. In the great majority of cases, pathologies associated with each other (cardiovascular, respiratory, neurological), while in other cases we can treat rare diseases or syndromes. It’s considered exceptional the simultaneous presence of “rare” pathologies in a single patient. This exceptionality has been a push to treat a patient as a “unique” asking for help to deeper studies of pharmacogenetics. Our case reports the management of a patient with Ehlers-Danlos syndrome (EDS) and Multiple Chemical Sensitivity (MCS), undergoing a total thyroidectomy.We found several problems, and we tried to find effective solutions for the management of the patient during the whole peri-operative process, from a clinical, pharmacological and also from a surgical point of view.     

Psychiatric Assessment and Management of Clients Undergoing Cosmetic Surgery: Overview and Need for an Integrated Approach

Background  Psychiatric disorders are more common among people undergoing cosmetic procedures than the general population and evaluating mental health can be cumbersome for plastic surgeons. We aim to summarize the available literature in this regard and propose an integrated approach to psychiatric assessment and management of mental health issues among this group. Methods  Electronic search of MEDLINE, Google Scholar, and PsycINFO databases was done to identify relevant peer-reviewed English language articles from inception till April 2020. Generated abstracts were screened for their eligibility. Included articles were grouped according to their thematic focus under the following headings; prevalence of psychiatric morbidity among clients posted for cosmetic surgery, assessment tools, and management of psychiatric morbidity in relation to undergoing cosmetic surgery. Results  A total of 120 articles were reviewed. The prevalence of psychiatric disorder in patients undergoing cosmetic surgery was 4 to 57% for body dysmorphic disorder (BDD); the corresponding figures for depression, anxiety, and personality disorder were 4.8 to 25.8, 10.8 to 22, and 0 to 53%, respectively. A range of tools have been used to assess these disorders and specific measures are also available to assess clinical outcomes following surgery. Screening for these disorders is essential to prevent unnecessary surgical procedures, as well as to ensure timely management of the psychiatric comorbidity. Conclusion  Psychiatric morbidity is a common concomitant in cosmetic surgery. A structured and integrated approach to evaluation and management of psychiatric morbidity will help to optimize postsurgical outcomes.     

“Acute postoperative open abdominal wall”: Nosological concept and treatment implications

The so-called “burst abdomen” has been described for many years and is a well-known clinical condition, whereas the concept of the “open abdomen” is relatively new. In clinical practice, both nosological entities are characterized by a complex spectrum of symptoms apparently disconnected, which in many cases poses a great challenge for surgical repair. In order to assess the management of these disorders in a more comprehensive and integral fashion, the concept of “acute postoperative open abdominal wall” (acute POAW) is presented, which in turn can be divided into “intentional” or planned acute POAW and “unintentional” or unplanned POAW. The understanding of the acute POAW as a single clinical process not only allows a better optimization of the therapeutic approach in the surgical repair of abdominal wall-related disorders, but also the stratification and collection of data in different patient subsets, favoring a better knowledge of the wide spectrum of conditions involved in the surgical reconstruction of the abdominal wall.     

Pediatric facial burns: Is facial transplantation the new reconstructive psychosurgery?

INTRODUCTION:

Current pediatric burn care has resulted in survival being the expectation for most children. Composite tissue allotransplantation in the form of face or hand transplantation may present opportunities for reconstructive surgery of patients with burns. The present paper addresses the question “Could facial transplantation be of therapeutic benefit in the treatment of pediatric burns associated with facial disfigurement?”

METHODS:

Therapeutic benefit of facial transplantation was defined in terms of psychiatric adjustment and quality of life (QOL). To ascertain therapeutic benefit, studies of pediatric burn injury and associated psychiatric adjustment and QOL in children, adolescents and adults with pediatric burns, were reviewed.

RESULTS:

Pediatric burn injury is associated with anxiety disorders, including post-traumatic stress disorder and depressive disorders. Many patients with pediatric burns do not routinely access psychiatric care for these disorders, including those for psychiatric assessment of suicidal risk. A range of QOL outcomes were reported; four were predominantly satisfactory and one was predominantly unsatisfactory.

DISCUSSION:

Facial transplantation may reduce the risk of depressive and anxiety disorders other than post-traumatic stress disorder. Facial transplantation promises to be the new reconstructive psychosurgery, because it may be a surgical intervention with the potential to reduce the psychiatric suffering associated with pediatric burns. Furthermore, patients with pediatric burns may experience the stigma of disfigurement and psychiatric conditions. The potential for improved appearance with facial transplantation may reduce this ‘dual stigmata’. Studies combining surgical and psychiatric research are warranted.     

Obsessive-compulsive disorder: identification, neurobiology, and treatment

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder. It may go unrecognized, however, as many patients are embarrassed by their symptoms and are thus reluctant to report them. Recent research findings on OCD point to neurologic dysfunction in the circuitry of the orbitofrontal cortex and basal ganglia. The advent of the use of serotonin reuptake inhibitors (SRIs) as well as behavioral therapy has greatly improved treatment outcomes for patients with OCD. Given the likelihood that these patients are encountered in primary care consultations, physicians have the opportunity to play a crucial role in the early identification and proper treatment of OCD.     

Transcranial magnetic stimulation

TMS is a powerful new tool with extremely interesting research and therapeutic potentials. Further understanding of the ways by which TMS changes neuronal function, especially as a function of its use parameters, will improve its ability to answer neuroscience questions as well as to treat diseases. Because of its noninvasiveness, it does not readily fit under the umbrella of neurosurgery. Nevertheless, it is important for neurosurgeons to be aware of TMS, because findings from TMS studies will have implications for neurosurgical approaches like DBS and VNS. Indeed, it is possible to think of using TMS as a potential noninvasive initial screening tool to identify whether perturbation of a circuit has short-term clinical effects. In the example of chronic refractory depression or OCD, which is generally a chronic illness, it might then follow that rather than having daily or weekly TMS for the rest of their lives, patients would have DBS electrodes implanted in the same circuit. Whatever road the future takes, TMS is an important new tool that will likely be of interest to neurosurgeons over the next 20 years and perhaps even longer.     

Mechanisms of action of high-frequency deep brain stimulation. A review of the literature and current concepts

High-frequency deep brain stimulation (HF-DBS) has become a widely used therapeutic method in the field of movement disorders for the treatment of Parkinson's disease, essential tremor or dystonia. New targets and indications are under evaluation in several other conditions such as cluster headache, obesity, epilepsy or psychiatric diseases (depression, OCD). However, the mechanisms of action of HF-DBS remain poorly understood. Herein we present a review of the literature and our current view of the question. The first part deals with the effects of stimulation itself on the different parts of the neuron and tries to answer the question of what is actually stimulated by DBS (cell bodies, dendrites or axons). The second part is devoted to the ortho- and antidromic effects of the stimulation. The third part more specifically focuses on the case of subthalamic nucleus stimulation. The target axons in the subthalamic area are discussed in the light of recent optogenetic studies. In conclusion, HF-DBS leads to a kind of functional deafferentation of the stimulated structure and to the modulation of cortical activity (both ortho and antidromically). Which effects are relevant to the therapeutic effects of DBS is still unclear. Further investigations are required especially regarding the corticosubthalamic pathways.     

Review of long-term results of stereotactic psychosurgery

Stereotactic psychosurgery is an effective method for treating some medically intractable psychiatric illnesses. However, it is unfamiliar and the long-term clinical results have not been reported in Asia. The long-term results of psychosurgery are evaluated and the neuroanatomical basis is discussed. Twenty-one patients underwent stereotactic psychosurgery for medically intractable psychiatric illnesses since 1993. All were referred from psychiatrists for these disorders. Two patients showed aggressive behavior, 12 had obsessive-compulsive disorder (OCD), and seven had depression with anxiety disorders. Bilateral amygdalotomy and subcaudate tractotomy were performed for aggressive behavior, limbic leucotomy was performed for OCD, and subcaudate tractotomy with or without cingulotomy was performed for depression with anxiety. OCD was evaluated with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the visual analogue scale, the Clinical Global Impression Scale, and the Overt Aggression Scale (OAS). The Mini-Mental State Examination and the Wechsler Adult Intelligence Scale-Revised were used for the evaluation of aggressive behavior. The 17-item Hamilton Depression Rating Scale (HAMD) was used for evaluation of depression. Ventriculography was used in the first seven patients and magnetic resonance imaging-guided stereotaxy was used in the recent 14 cases for localization of the target. The lesions were made with a radiofrequency lesion generator. OAS scores in the two patients with aggressive behavior during follow up declined from 8 to 2 with clinical improvement. All 12 patients with OCD returned to their previous life and showed the mean YBOCS scores decreased from 34 to 3. Ten patients with OCD could be followed up (mean 45 months). All patients returned to their previous social life. In seven patients with depression with anxiety, HAMD scores declined from 28.5 to 16.5. There was no operative mortality and no significant morbidity except for one case of mild transient urinary incontinence. These long-term results indicate that stereotactic psychosurgery is a safe and effective method of treating some medically intractable psychiatric illnesses.